Displaying publications 1 - 20 of 32 in total

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  1. Sulaiman MR, Zakaria ZA, Mohamad AS, Ismail M, Hidayat MT, Israf DA, et al.
    Pharm Biol, 2010 Aug;48(8):861-8.
    PMID: 20673172 DOI: 10.3109/13880200903302820
    Alpinia conchigera Griff. (Zingiberaceae), locally known to the Malays as "lengkuas ranting", is native to Peninsular Malaysia. The Malays traditionally used it to treat infection and rashes, and as a health drink. This study evaluated the analgesic and anti-inflammatory activities of the ethanol extract of A. conchigera rhizomes in mice and rats, respectively. The analgesic activity was elucidated using the acetic acid-induced writhing test, hot plate test, and formalin test, while the anti-inflammatory activity was determined using carrageenan-induced paw edema. The extract (30, 100, and 300 mg/kg) given intraperitoneally (i.p.) exhibited antinociceptive and anti-inflammatory activities in all tests used. The range of percentage of analgesia obtained for all doses of extract in the writhing test was 50-92%, and in the early and late phases of the formalin test was 25-62% and 63-98%, respectively. In addition, naloxone (5 mg/kg) given subcutaneously (s.c.) was found to reverse the extract (300 mg/kg)-induced antinociceptive activity in the writhing, hot plate, and formalin tests. Based on the results obtained, it can be concluded that the ethanol extract of A. conchigera rhizomes possessed a peripheral and central antinociceptive activity that was mediated, in part, via the opioid receptor, as well as anti-inflammatory activity.
  2. Saim L, Mohamad AS, Ambu VK
    Int J Pediatr Otorhinolaryngol, 1994 Jan;28(2-3):241-6.
    PMID: 8157425
    Congenital lobar emphysema has been described under various designations. Although the etiology is not clear, some form of bronchial obstruction has been documented in about 50% of the patients. A rare case of congenital lobar emphysema with a membranous septum in the left main bronchus is described. Although prompt lobectomy has been the treatment of choice in most cases, this case demonstrates the importance of early bronchoscopy to exclude treatable intra luminal abnormalities.
  3. Subramaniyan M, Yee A, Hairi FM, Kaai SC, Nordin ASA, Danaee M, et al.
    J Ethn Subst Abuse, 2022 Sep 21.
    PMID: 36129734 DOI: 10.1080/15332640.2022.2123421
    The Malaysian government reinforced smoking restrictions at public venues to protect nonsmokers from secondhand smoke (SHS) exposure. This study examined whether smokers' reports about smoking restrictions and psychosocial beliefs were associated with quit intentions among Malaysian smokers. Data from 1047 cigarette smokers (103 females and 944 males) aged 18 and older from the 2020 International Tobacco Control (ITC) Malaysia Wave 1 Survey were analyzed with bivariate and multivariable logistic regression models. Most Malaysian smokers (85.2%) reported having quit intentions. Smoking was completely restricted in 34.8% of the nighttime venues, 85.3% of air-conditioned (AC) food and beverage (F&B) venues (restaurants, food courts, coffee shops), 87.3% of non-AC F&B, and 69.4% of indoor workplaces. Smokers who visited nighttime entertainment venues where smoking was fully restricted were less likely to have quit intentions. There was no significant association found with quit intentions for smokers who visited AC and non-AC F&B venues and indoor workplaces where smoking was fully restricted. All five psychosocial beliefs assessed, age, and education were positively associated with quit intentions. Malaysian smokers are interested in quitting and psychosocial beliefs were positively associated with quit intentions. There is a need for the Malaysian government to implement and reinforce comprehensive smoking restrictions in all public venues and indoor workplaces to protect nonsmokers from SHS exposure and to encourage smokers to think about quitting, which may influence their quit intentions.
  4. Wai YZ, Ng QX, Adnan TH, Chong YY, Mohamad AS, Goh PP
    Med J Malaysia, 2021 Nov;76(6):884-892.
    PMID: 34806678
    INTRODUCTION: Few studies have reported the impact of preoperative interocular discrepancy in optical biometry (axial length, corneal power, white-to-white, central corneal thickness) on postoperative refractive outcomes. This study aims to investigate any predictive value of preoperative optical biometry differences between eyes on postoperative refractive outcomes.

    MATERIALS AND METHODS: A retrospective cohort study of patients who have undergone optical biometry measurement before unilateral phacoemulsification in the Queen Elizabeth Hospital, Sabah, Malaysia from 2018 to 2020. Biometry data of interest includes axial length (AL), keratometry(K), white-to-white (WTW) and central corneal thickness (CCT). The postoperative outcomes of interest were the patient's preoperative refractive target, postoperative best-corrected visual acuity (BCVA), postoperative refractive outcomes, and optical biometry prediction error.

    RESULTS: The interocular biometry discrepancies which were associated with higher odds of prediction error >0.5D from the refractive target were Interocular Corneal Power Difference (IKD)-average≥0.8 D (Odds Ratio, OR=1.97; 95% Confidence Intervals, 95%CI: 1.06, 3.67) and Interocular WTW Difference ≥1.5 mm (OR=2.77; 95%CI: 1.11, 6.92). In cases with prediction error >1.0D, the measurements were Interocular AL Difference ≥0.4 mm (OR=2.99; 95%CI: 1.11, 8.06), IKD flat≥0.4D (OR=2.76; 95%CI: 1.31, 5.82) and Interocular CCT Difference ≥15μm (OR=3.53; 95%CI: 1.29, 9.64).

    CONCLUSION: Interocular axial length difference ≥0.4mm and interocular central corneal thickness difference ≥15μm are associated with refractive error >1.0D from the pre-operative target. Interocular average corneal power difference ≥0.8D and interocular white-to-white difference ≥1.5mm have higher odds of refractive drift >0.5D from the refractive aim. The above cutoff values help clinicians to identify which patients have a higher risk of refractive shift post-cataract surgery and counsel the patient before cataract operation.

  5. Wai YZ, Fiona Chew LM, Mohamad AS, Ang CL, Chong YY, Adnan TH, et al.
    Int J Ophthalmol, 2018;11(10):1685-1690.
    PMID: 30364221 DOI: 10.18240/ijo.2018.10.17
    AIM: To report the incidence, risk factors and visual outcomes for postoperative endophthalmitis (POE) based on 7-year data from the Malaysian Ministry of Health Cataract Surgery Registry (MOH CSR).

    METHODS: Data was collected from the web-based MOH CSR. All consecutive cataract surgery patients from 1st June 2008 to 31st December 2014 were identified. Exclusion criteria were traumatic cataract or previous ocular surgery. Demographic data, ocular co-morbidities, intraoperative details and postoperative visual acuity (VA) at final ophthalmological follow-up were noted. All eyes were taken for analysis. Subjects with POE were compared against subjects with no POE for risk factor assessment using multiple logistic regressions.

    RESULTS: A total of 163 503 subjects were screened. The incidence of POE was 0.08% (131/163 503). Demographic POE risk factors included male gender (OR: 2.121, 95%CI: 1.464-3.015) and renal disease (OR: 2.867, 95%CI: 1.503-5.467). POE risk increased with secondary causes of cataract (OR: 3.562, 95%CI: 1.740-7.288), uveitis (OR: 11.663, 95%CI: 4.292-31.693) and diabetic retinopathy (OR: 1.720, 95%CI: 1.078-2.744). Intraoperative factors reducing POE were shorter surgical time (OR: 2.114, 95%CI: 1.473-3.032), topical or intracameral anaesthesia (OR: 1.823, 95%CI: 1.278-2.602), posterior chamber intraocular lens (PCIOL; OR: 4.992, 95%CI: 2.689-9.266) and foldable IOL (OR: 2.276, 95%CI: 1.498-3.457). POE risk increased with posterior capsule rupture (OR: 3.773, 95%CI: 1.915-7.432) and vitreous loss (OR: 3.907, 95%CI: 1.720-8.873). Postoperative VA of 6/12 or better was achieved in 15.27% (20/131) subjects with POE.

    CONCLUSION: This study concurs with other studies regarding POE risk factors. Further strengthening of MOH CSR data collection process will enable deeper analysis and optimization of POE treatment.

  6. Sulaiman MR, Perimal EK, Akhtar MN, Mohamad AS, Khalid MH, Tasrip NA, et al.
    Fitoterapia, 2010 Oct;81(7):855-8.
    PMID: 20546845 DOI: 10.1016/j.fitote.2010.05.009
    The anti-inflammatory activity of zerumbone (1), a natural cyclic sesquiterpene isolated from Zingiber zerumbet Smith was investigated using carrageenan-induced paw edema and cotton pellet-induced granuloma tissue formation test in mice. It was demonstrated that intraperitoneal administration of 1 at a dose of 5, 10, 50 and 100 mg/kg produced significant dose-dependent inhibition of paw edema induced by carrageenan. It was also demonstrated that 1 at similar doses significantly suppressed granulomatous tissue formation in cotton pellet-induced granuloma test.
  7. Sulaiman MR, Zakaria ZA, Abdul Rahman A, Mohamad AS, Desa MN, Stanslas J, et al.
    Biol Res Nurs, 2010 Jan;11(3):293-301.
    PMID: 19689990 DOI: 10.1177/1099800409343311
    The current study was performed to evaluate the antinociceptive and antiedematogenic properties of andrographolide isolated from the leaves of Andrographis paniculata using two animal models. Antinociceptive activity was evaluated using the acetic acid- induced writhing and the hot-plate tests, while antiedematogenic activity was measured using the carrageenan-induced paw edema test. Subcutaneous (s.c.) administration of andrographolide (10, 25, and 50 mg/kg) did not affect the motor coordination of the experimental animals but produced significant (p < .05) antinociceptive activity when assessed using both tests. However, 2 mg/kg naloxone failed to affect the 25 mg/kg andrographolide activity in both tests, indicating that the activity was modulated via nonopioid mechanisms. Furthermore, andrographolide showed significant (p < .05) antiedematogenic activity. In conclusion, the results obtained suggest that andrographolide has antinociceptive and antiedematogenic activities; it may be useful for treating pain and inflammation once human studies are conducted.
  8. Harasstani OA, Moin S, Tham CL, Liew CY, Ismail N, Rajajendram R, et al.
    Inflamm Res, 2010 Sep;59(9):711-21.
    PMID: 20221843 DOI: 10.1007/s00011-010-0182-8
    OBJECTIVES: We evaluated several flavonoid combinations for synergy in the inhibition of proinflammatory mediator synthesis in the RAW 264.7 cellular model of inflammation.

    METHODS: The inhibitory effect of chrysin, kaempferol, morin, silibinin, quercetin, diosmin and hesperidin upon nitric oxide (NO), prostaglandin E(2) (PGE(2)) and tumour necrosis factor-alpha (TNF-alpha) secretion from the LPS-induced RAW 264.7 monocytic macrophage was assessed and IC(50) values obtained. Flavonoids that showed reasonable inhibitory effects in at least two out of the three assays were combined in a series of fixed IC(50) ratios and reassessed for inhibition of NO, PGE(2) and TNF-alpha. Dose-response curves were generated and interactions were analysed using isobolographic analysis.

    RESULTS: The experiments showed that only chrysin, kaempferol, morin, and silibinin were potent enough to produce dose-response effects upon at least two out of the three mediators assayed. Combinations of these four flavonoids showed that several combinations afforded highly significant synergistic effects.

    CONCLUSIONS: Some flavonoids are synergistic in their anti-inflammatory effects when combined. In particular chrysin and kaempferol significantly synergised in their inhibitory effect upon NO, PGE(2) and TNF-alpha secretion. These findings open further avenues of research into combinatorial therapeutics of inflammatory-related diseases and the pharmacology of flavonoid synergy.

  9. Tham CL, Liew CY, Lam KW, Mohamad AS, Kim MK, Cheah YK, et al.
    Eur J Pharmacol, 2010 Feb 25;628(1-3):247-54.
    PMID: 19958764 DOI: 10.1016/j.ejphar.2009.11.053
    Curcumin is a highly pleiotropic molecule with significant regulatory effects upon inflammation and inflammatory related diseases. However curcumin has one major important limitation in which it has poor bioavailability. Design of synthetic structural derivatives of curcumin is but one approach that has been used to overcome its poor bioavailability while retaining, or further enhancing, its drug-like effects. We have synthesized a series of curcumin analogues and describe the effects of 2,6-bis-4-(hydroxyl-3-methoxy-benzylidine)-cyclohexanone or BHMC upon nitric oxide and cytokine synthesis in cellular models of inflammation. BHMC showed a significant dose-response inhibitory action upon the synthesis of NO and we have shown that this effect was due to suppression of both iNOS gene and enzyme expression without any effects upon scavenging of nitrite. We also demonstrated that BHMC has a very minimal effect upon iNOS activity with no effect at all upon the secretion of PGE(2) but has a strong inhibitory effect upon MCP-1 and IL-10 secretion and gene expression. Secretion and gene expression of TNF-alpha and IL-6 were moderately inhibited whereas IL-8 and IL-1beta were not altered. We conclude that BHMC selectively inhibits the synthesis of several inflammatory mediators. BHMC should be considered a promising drug lead for preclinical and further pharmacological studies.
  10. Sulaiman MR, Zakaria ZA, Adilius M, Mohamad AS, Ismail M, Israf DA
    Methods Find Exp Clin Pharmacol, 2009 May;31(4):241-7.
    PMID: 19557202 DOI: 10.1358/mf.2009.31.4.1371198
    The ethanolic extract of Alpinia conchigera Griff. leaves (EACL) was evaluated for its antinociceptive and anti-inflammatory activities in several in vivo experimental models. Antinociceptive activity was determined using the acetic acid-induced abdominal writhing test, the hot plate test and the formalin test. Anti-inflammatory activity was determined using the carrageenan-induced paw edema test. The extract (30, 100 and 300 mg/kg i.p.) was found to possess significant, dose-dependent inhibitory activity in all test models. In addition, the antinociceptive effect of the extract in the acetic acid-induced writhing and hot plate tests was reversed by naloxone, suggesting that this activity is mediated through activation of the opioid system. These findings suggest that EACL presents notable analgesic and anti-inflammatory activities, which support its folkloric use for painful and inflammatory conditions.
  11. Sulaiman MR, Hussain MK, Zakaria ZA, Somchit MN, Moin S, Mohamad AS, et al.
    Fitoterapia, 2008 Dec;79(7-8):557-61.
    PMID: 18672036 DOI: 10.1016/j.fitote.2008.06.005
    The aqueous extract of Ficus deltoidea leaves was evaluated for possible antinociceptive activity in three models of nociception, namely, acetic acid-induced abdominal writhing, formalin and hot plate test. The results of the present study showed that intraperitoneal administration of the F. deltoidea leaves aqueous extract at the dose of 1, 50 and 100 mg/kg, 30 min prior to pain induction produced significant dose-dependent antinociceptive effect in all the models used, which indicating the presence of both central and peripherally mediated activities. Furthermore, the antinociceptive effect of the extract in the formalin and hot plate test was reversed by the non-selective opioid receptor antagonist naloxone suggesting that the endogenous opioid system is involved in its analgesic mechanism of action. Thus, the present results demonstrated that F. deltoidea leaves aqueous extract contains pharmacologically active constituents which possess antinociceptive activity justifying its popular therapeutic use in treating conditions associated with the painful conditions.
  12. Liew CY, Tham CL, Lam KW, Mohamad AS, Kim MK, Cheah YK, et al.
    Immunopharmacol Immunotoxicol, 2010 Sep;32(3):495-506.
    PMID: 20109039 DOI: 10.3109/08923970903575708
    HMP [3-(2-hydroxyphenyl)-1-(5-methyl-furan-2-y-l) propenone] was evaluated for its ability to inhibit the synthesis of major proinflammatory mediators and cytokines in interferon-gamma (IFN-gamma)- and lipopolysaccharide (LPS)-induced RAW 264.7 cells and phorbol myristate acetate (PMA)-differentiated/LPS-induced U937 cells. HMP suppressed the production of nitric oxide (NO) with significant inhibitory effects at doses as low as 0.78 microM (P < 0.05). Prostaglandin E2 (PGE2) secretion was also inhibited at doses of 12.5 microM and above (P < 0.01). The secretion of both TNF-alpha and IL-6 were only inhibited at the highest dose used (25 microM; P < 0.001). IL-1beta secretion was also inhibited from 12.5 microM onwards (P < 0.01). This inhibition was demonstrated to be caused by down-regulation of inducible enzymes, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2), without direct effect upon iNOS or COX-2 enzyme activity. HMP only inhibited iNOS (P < 0.001) and IL-1beta (P < 0.05) gene expression at the highest tested concentration. HMP did not affect the secretion of chemokines IL-8 and monocyte chemotactic protein-1 (MCP-1) and the anti-inflammatory cytokine IL-10. The most striking effect of HMP was its NO inhibitory activity and therefore we conclude that HMP is a selective inhibitor of iNOS.
  13. Sulaiman MR, Mohd Padzil A, Shaari K, Khalid S, Shaik Mossadeq WM, Mohamad AS, et al.
    J Biomed Biotechnol, 2010;2010:937642.
    PMID: 21274262 DOI: 10.1155/2010/937642
    Melicope ptelefolia is a medicinal herb commonly used in Malaysia to treat fever, pain, wounds, and itches. The present study was conducted to evaluate the antinociceptive activity of the Melicope ptelefolia ethanolic extract (MPEE) using animal models of nociception. The antinociceptive activity of the extract was assessed using acetic acid-induced abdominal writhing, hot-plate, and formalin-induced paw licking tests. Oral administration of MPEE produced significant dose-dependent antinociceptive effects when tested in mice and rats using acetic acid-induced abdominal constriction test and on the second phase of the formalin-induced paw licking test, respectively. It was also demonstrated that MPEE had no effect on the response latency time to the heat stimulus in the thermal model of the hot-plate test. In addition, the antinociception produced by MPEE was not blocked by naloxone. Furthermore, oral administration of MPEE did not produce any effect in motor performance of the rota-rod test and in acute toxicity study no abnormal behaviors as well as mortality were observed up to a dose level of the extract of 5 g/kg. These results indicated that MPEE at all doses investigated which did not produce any sedative and toxic effects exerted pronounce antinociceptive activity that acts peripherally in experimental animals.
  14. Abu Bakar NA, Sulaiman MR, Lajis N, Akhtar MN, Mohamad AS
    J Pharm Bioallied Sci, 2020 Nov;12(Suppl 2):S711-S717.
    PMID: 33828366 DOI: 10.4103/jpbs.JPBS_344_19
    Introduction: Pain is a major global health issue, where its pharmacotherapy prompts unwanted side effects; hence, the development of effective alternative compounds from natural derivatives with lesser side effects is clinically needed. Chalcone; the precursors of flavonoid, and its derivatives have been widely investigated due to its pharmacological properties.

    Objective: This study addressed the therapeutic effect of 3-(2,5-dimethoxyphenyl)-1-(5-methyl furan-2-yl) prop-2-en-1-one (DMPF-1); synthetic chalcone derivative, on antinociceptive activity in vivo.

    Materials and Methods: The antinociceptive profile was evaluated using acetic-acid-induced abdominal writhing, hot plate, and formalin-induced paw licking test. Capsaicin, phorbol 12-myristate 12 acetate (PMA), and glutamate-induced paw licking test were carried out to evaluate their potential effects toward different targets.

    Results: It was shown that the doses of 0.1, 0.5, 1, and 5 mg/kg of DMPF-1 given via intraperitoneal injection showed significant reduction in writhing responses and increased the latency time in hot-plate test where reduced time spent on licking the injected paw in formalin and dose contingency inhibition was observed. The similar results were observed in capsaicin, PMA, and glutamate-induced paw licking test. In addition, the challenge with nonselective opioid receptor antagonist (naloxone) aimed to evaluate the involvement of the opioidergic system, which showed no reversion in analgesic profile in formalin and hot-plate test.

    Conclusion: Collectively, this study showed that DMPF-1 markedly inhibits both peripheral and central nociception through the mechanism involving an interaction with vanilloid and glutamatergic system regardless of the activation of the opioidergic system.

  15. Al-Yahya SN, Baki MM, Saad SM, Azman M, Mohamad AS
    Ann Saudi Med, 2016 8 2;36(4):292-7.
    PMID: 27478916 DOI: 10.5144/0256-4947.2016.292
    A systematic review on laryngopyoceles across Ovid, PubMed, and Google Scholar database was conducted. A total of 61 papers published between 1952 and 2015 were found. Of these, 23 cases written in English, which described the number of cases, surgical approaches, resort to tracheostomy, complications, and outcomes, were shortlisted. Four cases of laryngopyoceles were managed endoscopically using a cold instrument, microdebrider, or laser. Eighteen cases were operated via an external approach, and 1 case applied both approaches. One of 4 endoscopic and 10 of 18 external approaches involved tracheostomy. The present study aimed to report a case of large mixed laryngopyocele that was successfully drained and marsupialized endoscopically using suction diathermy without requiring tracheostomy. Management using suction diathermy for excision and marsupialization of a laryngopyocele has never been reported and can be recommended as a feasible method due to its widespread availability. In the presence of a large laryngopyocele impeding the airway, tracheostomy may be averted in a controlled setting.

    SIMILAR CASES PUBLISHED: None specified.

  16. Chia JSM, Omar Farouk AA, Mohamad AS, Sulaiman MR, Perimal EK
    Biomed Pharmacother, 2016 Oct;83:1303-1310.
    PMID: 27570173 DOI: 10.1016/j.biopha.2016.08.052
    Zerumbone, a bioactive sesquiterpene isolated from Zingiber zerumbet (Smith), has shown to exert antiallodynic and antihyperalgesic effects in neuropathic pain mice model in our recent study. The mechanism through which zerumbone alleviates neuropathic pain has yet to be elucidated. Thus, this study aimed to determine whether the serotonergic system, part of the descending pain modulation pathway, contributes to the antineuropathic effect of zerumbone. Participation of the serotonergic system in zerumbone-induced antiallodynia and antihyperalgesia was assessed using Dynamic Plantar Aesthesiometer von Frey test and Hargreaves plantar test respectively in chronic-constriction injury mice model. Administration of ρ-chlorophenylalanine (PCPA, 100mg/kg, i.p.) for four consecutive days to deplete serotonin (5-HT) prior to zerumbone administration blocked the antiallodynic and antihyperalgesic effects of zerumbone. Further investigation with 5-HT receptor antagonists methiothepin (5-HT1/6/7 receptor antagonist, 0.1mg/kg), WAY-100635 (5-HT1A receptor antagonist, 1mg/kg), isamoltane (5-HT1B receptor antagonist, 2.5mg/kg), ketanserin (5-HT2A receptor antagonist, 0.3mg/kg) and ondansetron (5-HT3 receptor antagonist, 0.5mg/kg) managed to significantly attenuate antiallodynic and antihyperalgesic effects of zerumbone (10mg/kg). These findings demonstrate that zerumbone alleviates mechanical allodynia and thermal hyperalgesia through the descending serotonergic system via 5-HT receptors 1A, 1B, 2A, 3, 6 and 7 in chronic constriction injury neuropathic pain mice.
  17. Mohamad AS, Rejab E, Said H
    Med J Malaysia, 1989 Jun;44(2):174-7.
    PMID: 2626128
    A case of carotid body tumour is presented. Pathology, diagnostic investigations, modalities of treatment and prognosis are discussed. With greater awareness of this condition and improvement in diagnostic investigations and surgical techniques, the outlook in managing this condition should be better.
  18. Mohamad AS, Hamzah R, Selvaratnam V, Yegapan S, Sathar J
    Hematol Rep, 2018 Sep 05;10(3):7210.
    PMID: 30344984 DOI: 10.4081/hr.2018.7210
    Human hemoglobin of G-Makassar variant has been reported very rarely with Beta Thalassemia. In year 1969 Hb GMakassar was first identified in Makassar, Sulawesi (Celebes), Republic of Indonesia. The disease was first published in 1969 and 33 years later it has been reported at a family of Thailand origin. We report a 45-yearold Malay man who was investigated for anemia and thrombocytopenia then diagnosed with Hb G-Makassar. This finding describes as a new Hemoglobin GMakassar discovered in Malaysia after 14 years diagnosed in Thailand.
  19. Kamaldin MN, Akhtar MN, Mohamad AS, Lajis N, Perimal EK, Akira A, et al.
    Molecules, 2013 Apr 10;18(4):4209-20.
    PMID: 23612473 DOI: 10.3390/molecules18044209
    Previous studies have shown that systemic administration of 6'-hydroxy-2',4'-dimethoxychalcone (flavokawin B, FKB) exerts significant peripheral and central antinociceptive effects in laboratory animals. However, the mechanisms underlying these peripheral and central antinociceptive effects have yet to be elucidated. Therefore, the objective of the present study was to evaluate the participation of nitric oxide (NO)/cyclic guanosine monophosphate (cGMP)/potassium (K+) channels pathway in the peripheral antinociception induced by FKB. It was demonstrated that intraplantar (i.pl.) administration of FKB (150, 250, 375 and 500 µg/paw) resulted in dose-dependent peripheral antinociception against mechanical hyperalgesia in carrageenan-induced hyperalgesia test model in rats. The possibility of FKB having either a central or a systemic effect was excluded since administration of FKB into the right paw did not elicit antinociception in the contralateral paw. Furthermore, peripheral antinociception induced by FKB (500 µg/paw) was significantly reduced when L-arginine (25 µg/paw, i.pl.), Oxadiazolo[4,3-a]quinoxalin-1-one (ODQ; 50 µg/paw, i.pl.), glibenclamide (300 µg/paw, i.pl.), tetraethylammonium (300 µg/paw, i.pl.) and charybdotoxin (3 µg/paw, i.pl.) were injected before treatment. Taken together, our present data suggest that FKB elicits peripheral antinociception when assessed in the mechanical hyperalgesia induced by carrageenan. In addition, it was also demonstrated that this effect was mediated through interaction of the NO/cGMP/K+ channels signaling pathway.
  20. Ming-Tatt L, Khalivulla SI, Akhtar MN, Mohamad AS, Perimal EK, Khalid MH, et al.
    Basic Clin Pharmacol Toxicol, 2012 Mar;110(3):275-82.
    PMID: 21967232 DOI: 10.1111/j.1742-7843.2011.00804.x
    This study investigated the potential antinociceptive efficacy of a novel synthetic curcuminoid analogue, 2,6-bis-(4-hydroxy-3-methoxybenzylidene)cyclohexanone (BHMC), using chemical- and thermal-induced nociception test models in mice. BHMC (0.03, 0.1, 0.3 and 1.0 mg/kg) administered via intraperitoneal route (i.p.) produced significant dose-related inhibition in the acetic acid-induced abdominal constriction test in mice with an ID(50) of 0.15 (0.13-0.18) mg/kg. It was also demonstrated that BHMC produced significant inhibition in both neurogenic (first phase) and inflammatory phases (second phase) of the formalin-induced paw licking test with an ID(50) of 0.35 (0.27-0.46) mg/kg and 0.07 (0.06-0.08) mg/kg, respectively. Similarly, BHMC also exerted significant increase in the response latency period in the hot-plate test. Moreover, the antinociceptive effect of the BHMC in the formalin-induced paw licking test and the hot-plate test was antagonized by pre-treatment with the non-selective opioid receptor antagonist, naloxone. Together, these results indicate that the compound acts both centrally and peripherally. In addition, administration of BHMC exhibited significant inhibition of the neurogenic nociception induced by intraplantar injections of glutamate and capsaicin with ID(50) of 0.66 (0.41-1.07) mg/kg and 0.42 (0.38-0.51) mg/kg, respectively. Finally, it was also shown that BHMC-induced antinociception was devoid of toxic effects and its antinociceptive effect was associated with neither muscle relaxant nor sedative action. In conclusion, BHMC at all doses investigated did not cause any toxic and sedative effects and produced pronounced central and peripheral antinociceptive activities. The central antinociceptive activity of BHMC was possibly mediated through activation of the opioid system as well as inhibition of the glutamatergic system and TRPV1 receptors, while the peripheral antinociceptive activity was perhaps mediated through inhibition of various inflammatory mediators.
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